Randomized phase II/III study of 5-fluorouracil/l-leucovorin versus 5-fluorouracil/l-leucovorin plus paclitaxel administered to patients with severe peritoneal metastases of gastric cancer (JCOG1108/WJOG7312G)

• Published in: Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 2020-07, Vol.23 (4), p.677-688
• Main Authors: Nakajima, Takako Eguchi, Yamaguchi, Kensei, Boku, Narikazu, Hyodo, Ichinosuke, Mizusawa, Junki, Hara, Hiroki, Nishina, Tomohiro, Sakamoto, Takeshi, Shitara, Kohei, Shinozaki, Katsunori, Katayama, Hiroshi, Nakamura, Shinichiro, Muro, Kei, Terashima, Masanori
• Format: Article
• Language: English
• Subjects: 5-Fluorouracil; Abdominal Surgery; Adenocarcinoma; Anorexia; Ascites; Cancer Research; Chemotherapy; Cisplatin; Gastric cancer; Gastroenterology; Leukopenia; Medicine; Medicine & Public Health; Metastases; Metastasis; Oncology; Original Article; Paclitaxel; Peritoneum; Surgical Oncology; Survival; Toxicity
• ISSN: 1436-3291; 1436-3305
• DOI: 10.1007/s10120-020-01043-x

Background Oral fluoropyrimidine plus cisplatin is often not tolerated by patients with severe peritoneal metastases of gastric cancer. Combination of 5-fluorouracil (5-FU), l -leucovorin ( l -LV), and paclitaxel (FLTAX) has promising activity for such patients. We conducted a phase II/III study comparing FLTAX with 5-FU/ l -LV. Methods Eligibility criteria included: unresectable or recurrent gastric adenocarcinoma; 20–75 years; performance status (PS) 0–2; peritoneal metastases + ; massive ascites and/or inadequate oral intake; no prior chemotherapy. Patients were randomly assigned to receive 5-FU/ l -LV or FLTAX. The primary endpoint of phase III was overall survival: UMIN000010949. Results We enrolled 101 patients. Early deaths occurred in patients with PS 2 having massive ascites and inadequate oral intake simultaneously; the protocol was amended to exclude such patients. Median survival times were 6.1 and 7.3 months for the 5-FU/ l -LV and the FLTAX arms, respectively (HR 0.792; 80% CI 0.596–1.053; one-sided p  = 0.1445). FLTAX arm had longer progression-free survival (PFS) [1.9 vs 5.4 months (HR 0.64; 95% CI, 0.43–0.96; p  = 0.029)]. Grade 3/4 adverse events such as leucopenia and anorexia were more frequently observed in the 5-FU/ l -LV arm. In the 5-FU/ l -LV arm, two deaths were treatment-related. In the 5-FU/ l -LV and FLTAX arms, 12 and 3 deaths occurred within 30 days after the last protocol treatment, respectively. Conclusions Chemotherapy was indicated for patients with severe peritoneal metastases excluding patients with PS 2 having massive ascites and inadequate oral intake simultaneously. FLTAX did not confer a significant survival benefit but may be preferred because of longer PFS and acceptable toxicity.